{"id":"https://openalex.org/W7225397204","doi":"https://doi.org/10.3389/fcell.2026.1984644","title":"Metabolite-driven protein post-translational modifications: network mechanisms bridging metabolic sensing and functional regulation","display_name":"Metabolite-driven protein post-translational modifications: network mechanisms bridging metabolic sensing and functional regulation","publication_year":2026,"publication_date":"2026-11-06","ids":{"openalex":"https://openalex.org/W7225397204","doi":"https://doi.org/10.3389/fcell.2026.1984644"},"language":"en","primary_location":{"id":"doi:10.3389/fcell.2026.1984644","doi":"https://doi.org/10.3389/fcell.2026.1984644","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fcell.2026.1984644","pdf_url":"https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1984644/pdf","source":{"id":"https://openalex.org/S2596924766","display_name":"Frontiers in Cell and Developmental Biology","issn_l":"2296-634X","issn":["2296-634X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Cell and Developmental Biology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1984644/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5064359802","display_name":"Shuangcui Wang","orcid":"https://orcid.org/0000-0002-3685-517X","observed_orcids":["https://orcid.org/0000-0002-3685-517X"]},"institutions":[{"id":"https://openalex.org/I111381250","display_name":"Hebei Medical University","ror":"https://ror.org/04eymdx19","country_code":"CN","type":"education","lineage":["https://openalex.org/I111381250"]},{"id":"https://openalex.org/I4210088328","display_name":"Third Hospital of Hebei Medical University","ror":"https://ror.org/004eknx63","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210088328"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Shuangcui Wang","raw_affiliation_strings":["Department of Orthopedic Surgery, Hebei Medical University Third Hospital"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Orthopedic Surgery, Hebei Medical University Third Hospital","institution_ids":["https://openalex.org/I111381250","https://openalex.org/I4210088328"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5151801777","display_name":"Yue Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405279728","display_name":"Qilu Medical University","ror":"https://ror.org/01xbh9923","country_code":"CN","type":"education","lineage":["https://openalex.org/I4405279728"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yue Zhang","raw_affiliation_strings":["School of Rehabilitation Medicine, Qilu Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Rehabilitation Medicine, Qilu Medical University","institution_ids":["https://openalex.org/I4405279728"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5064359802"],"corresponding_institution_ids":["https://openalex.org/I111381250","https://openalex.org/I4210088328"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"14","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13157","display_name":"Cancer-related gene regulation","score":0.20759999752044678,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T13157","display_name":"Cancer-related gene regulation","score":0.20759999752044678,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11482","display_name":"RNA modifications and cancer","score":0.2013999968767166,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11884","display_name":"Redox biology and oxidative stress","score":0.09449999779462814,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/lactylation","display_name":"lactylation","score":0.7649999856948853},{"id":"https://openalex.org/keywords/succinylation","display_name":"succinylation","score":0.9940000176429749},{"id":"https://openalex.org/keywords/o-glcnacylation","display_name":"O-GlcNAcylation","score":0.9900000095367432},{"id":"https://openalex.org/keywords/metabolic-sensing","display_name":"metabolic sensing","score":0.8799999952316284},{"id":"https://openalex.org/keywords/chromatin-remodeling","display_name":"chromatin remodeling","score":0.7860000133514404},{"id":"https://openalex.org/keywords/protein-phase-separation","display_name":"protein phase separation","score":0.9800000190734863},{"id":"https://openalex.org/keywords/ptm-crosstalk","display_name":"PTM crosstalk","score":0.7450000047683716},{"id":"https://openalex.org/keywords/metabolic-disorders","display_name":"metabolic disorders","score":0.49399998784065247},{"id":"https://openalex.org/keywords/carcinogenesis","display_name":"carcinogenesis","score":0.7099999785423279},{"id":"https://openalex.org/keywords/immune-disorders","display_name":"immune disorders","score":0.8610000014305115},{"id":"https://openalex.org/keywords/biomarker-discovery","display_name":"biomarker discovery","score":0.640999972820282},{"id":"https://openalex.org/keywords/precision-intervention","display_name":"precision intervention","score":0.5080000162124634},{"id":"https://openalex.org/keywords/system-modeling","display_name":"system modeling","score":0.47099998593330383}],"concepts":[{"id":"https://openalex.org/C169822122","wikidata":"https://www.wikidata.org/wiki/Q230187","display_name":"Crosstalk","level":2,"score":0.6898999810218811},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5843999981880188},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4961000084877014},{"id":"https://openalex.org/C192989942","wikidata":"https://www.wikidata.org/wiki/Q68685","display_name":"Metabolic pathway","level":3,"score":0.49059998989105225},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.4307999908924103},{"id":"https://openalex.org/C158980903","wikidata":"https://www.wikidata.org/wiki/Q7899329","display_name":"Upstream and downstream (DNA)","level":3,"score":0.4034000039100647},{"id":"https://openalex.org/C70818257","wikidata":"https://www.wikidata.org/wiki/Q502671","display_name":"Metabolic control analysis","level":3,"score":0.3783000111579895},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.37310001254081726},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.3546000123023987},{"id":"https://openalex.org/C83640560","wikidata":"https://www.wikidata.org/wiki/Q180951","display_name":"Chromatin","level":3,"score":0.33230000734329224},{"id":"https://openalex.org/C21565614","wikidata":"https://www.wikidata.org/wiki/Q12149006","display_name":"Metabolomics","level":2,"score":0.3253999948501587},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.32359999418258667},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.32249999046325684},{"id":"https://openalex.org/C174348530","wikidata":"https://www.wikidata.org/wiki/Q188635","display_name":"Bridging (networking)","level":2,"score":0.3190000057220459},{"id":"https://openalex.org/C2991986269","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolic regulation","level":3,"score":0.31709998846054077},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.30000001192092896},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.29120001196861267},{"id":"https://openalex.org/C27153228","wikidata":"https://www.wikidata.org/wiki/Q3787274","display_name":"Transcriptional regulation","level":4,"score":0.2831999957561493},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.27900001406669617},{"id":"https://openalex.org/C101810790","wikidata":"https://www.wikidata.org/wiki/Q2263094","display_name":"Metabolic network","level":2,"score":0.2784999907016754},{"id":"https://openalex.org/C2776207758","wikidata":"https://www.wikidata.org/wiki/Q5303302","display_name":"Downstream (manufacturing)","level":2,"score":0.27079999446868896},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.2694999873638153},{"id":"https://openalex.org/C161078062","wikidata":"https://www.wikidata.org/wiki/Q1068690","display_name":"Functional genomics","level":5,"score":0.2671000063419342},{"id":"https://openalex.org/C150555746","wikidata":"https://www.wikidata.org/wiki/Q210973","display_name":"Cell signaling","level":3,"score":0.25540000200271606},{"id":"https://openalex.org/C124535831","wikidata":"https://www.wikidata.org/wiki/Q4915074","display_name":"Biomarker discovery","level":4,"score":0.25220000743865967}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.3389/fcell.2026.1984644","doi":"https://doi.org/10.3389/fcell.2026.1984644","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fcell.2026.1984644","pdf_url":"https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1984644/pdf","source":{"id":"https://openalex.org/S2596924766","display_name":"Frontiers in Cell and Developmental Biology","issn_l":"2296-634X","issn":["2296-634X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Cell and Developmental Biology","raw_type":"journal-article"},{"id":"pmh:oai:doaj.org/article:fe78252b6d7849f4a6d5938076157be8","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/fe78252b6d7849f4a6d5938076157be8","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Cell and Developmental Biology, Vol 14 (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fcell.2026.1984644","doi":"https://doi.org/10.3389/fcell.2026.1984644","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fcell.2026.1984644","pdf_url":"https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1984644/pdf","source":{"id":"https://openalex.org/S2596924766","display_name":"Frontiers in Cell and Developmental Biology","issn_l":"2296-634X","issn":["2296-634X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Cell and Developmental Biology","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.504800021648407}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225397204.pdf","grobid_xml":"https://content.openalex.org/works/W7225397204.grobid-xml"},"referenced_works_count":203,"referenced_works":["https://openalex.org/W2528945128","https://openalex.org/W2587947359","https://openalex.org/W2588699201","https://openalex.org/W2773645338","https://openalex.org/W2787693514","https://openalex.org/W2790931190","https://openalex.org/W2905288998","https://openalex.org/W2950853065","https://openalex.org/W3037861729","https://openalex.org/W3093675860","https://openalex.org/W3110525223","https://openalex.org/W3146401251","https://openalex.org/W3198467919","https://openalex.org/W3199242780","https://openalex.org/W3204159604","https://openalex.org/W3206144875","https://openalex.org/W3207366201","https://openalex.org/W3217140403","https://openalex.org/W4200175423","https://openalex.org/W4206661770","https://openalex.org/W4206915952","https://openalex.org/W4210588589","https://openalex.org/W4211188235","https://openalex.org/W4214501630","https://openalex.org/W4214615178","https://openalex.org/W4214647820","https://openalex.org/W4221104640","https://openalex.org/W4223942459","https://openalex.org/W4224947052","https://openalex.org/W4225146935","https://openalex.org/W4282922393","https://openalex.org/W4283743000","https://openalex.org/W4291570663","https://openalex.org/W4294710511","https://openalex.org/W4308916364","https://openalex.org/W4309412217","https://openalex.org/W4310209504","https://openalex.org/W4311700815","https://openalex.org/W4312348347","https://openalex.org/W4315703437","https://openalex.org/W4317549025","https://openalex.org/W4327951472","https://openalex.org/W4362471247","https://openalex.org/W4362716812","https://openalex.org/W4367319294","https://openalex.org/W4367626486","https://openalex.org/W4367627987","https://openalex.org/W4378575828","https://openalex.org/W4378781896","https://openalex.org/W4380576376","https://openalex.org/W4383998539","https://openalex.org/W4384938448","https://openalex.org/W4385064043","https://openalex.org/W4385703185","https://openalex.org/W4386022035","https://openalex.org/W4386048117","https://openalex.org/W4386698693","https://openalex.org/W4386886531","https://openalex.org/W4386898192","https://openalex.org/W4387344981","https://openalex.org/W4387566330","https://openalex.org/W4387745752","https://openalex.org/W4388048618","https://openalex.org/W4388075520","https://openalex.org/W4388481056","https://openalex.org/W4389514681","https://openalex.org/W4390238647","https://openalex.org/W4390587886","https://openalex.org/W4390618182","https://openalex.org/W4390671190","https://openalex.org/W4391521761","https://openalex.org/W4391541155","https://openalex.org/W4391654228","https://openalex.org/W4391747433","https://openalex.org/W4391848628","https://openalex.org/W4391970598","https://openalex.org/W4392004498","https://openalex.org/W4392192985","https://openalex.org/W4392231795","https://openalex.org/W4392236275","https://openalex.org/W4392461860","https://openalex.org/W4392581479","https://openalex.org/W4392657009","https://openalex.org/W4392956764","https://openalex.org/W4393038355","https://openalex.org/W4393199938","https://openalex.org/W4393280041","https://openalex.org/W4394575043","https://openalex.org/W4394879573","https://openalex.org/W4395037449","https://openalex.org/W4395465306","https://openalex.org/W4396665870","https://openalex.org/W4396778845","https://openalex.org/W4397022907","https://openalex.org/W4399480698","https://openalex.org/W4399678092","https://openalex.org/W4400126185","https://openalex.org/W4400344678","https://openalex.org/W4400588280","https://openalex.org/W4400589393","https://openalex.org/W4400593308","https://openalex.org/W4401728941","https://openalex.org/W4401828559","https://openalex.org/W4401832386","https://openalex.org/W4402459440","https://openalex.org/W4403006894","https://openalex.org/W4403424687","https://openalex.org/W4403497641","https://openalex.org/W4403628860","https://openalex.org/W4404225847","https://openalex.org/W4404311095","https://openalex.org/W4404659714","https://openalex.org/W4406150750","https://openalex.org/W4406231939","https://openalex.org/W4406326329","https://openalex.org/W4406639603","https://openalex.org/W4406874143","https://openalex.org/W4406918624","https://openalex.org/W4406935701","https://openalex.org/W4407329452","https://openalex.org/W4407409445","https://openalex.org/W4407708274","https://openalex.org/W4407911537","https://openalex.org/W4408253655","https://openalex.org/W4409181050","https://openalex.org/W4409192728","https://openalex.org/W4410051532","https://openalex.org/W4410280989","https://openalex.org/W4410844395","https://openalex.org/W4411127830","https://openalex.org/W4411205666","https://openalex.org/W4411487582","https://openalex.org/W4411665865","https://openalex.org/W4412056519","https://openalex.org/W4412393790","https://openalex.org/W4412640965","https://openalex.org/W4412764166","https://openalex.org/W4412990266","https://openalex.org/W4413015668","https://openalex.org/W4413094461","https://openalex.org/W4413138879","https://openalex.org/W4413425536","https://openalex.org/W4413825512","https://openalex.org/W4413835520","https://openalex.org/W4413912910","https://openalex.org/W4414085460","https://openalex.org/W4414161430","https://openalex.org/W4414299197","https://openalex.org/W4414500787","https://openalex.org/W4414691899","https://openalex.org/W4414933769","https://openalex.org/W4415082287","https://openalex.org/W4415247714","https://openalex.org/W4416003871","https://openalex.org/W4416121808","https://openalex.org/W4416704627","https://openalex.org/W4416718070","https://openalex.org/W4417032651","https://openalex.org/W4417085890","https://openalex.org/W4417222675","https://openalex.org/W7117251601","https://openalex.org/W7117260679","https://openalex.org/W7117460852","https://openalex.org/W7122805873","https://openalex.org/W7124564415","https://openalex.org/W7125099158","https://openalex.org/W7127038141","https://openalex.org/W7127318074","https://openalex.org/W7128913365","https://openalex.org/W7128917910","https://openalex.org/W7134954488","https://openalex.org/W7138869168","https://openalex.org/W7140144979","https://openalex.org/W7152673995","https://openalex.org/W7153197114","https://openalex.org/W7155902573","https://openalex.org/W7160040714","https://openalex.org/W7160105099","https://openalex.org/W7160534999","https://openalex.org/W7161061867","https://openalex.org/W7161127017","https://openalex.org/W7161543640","https://openalex.org/W7161572467","https://openalex.org/W7162798223","https://openalex.org/W7163922803","https://openalex.org/W7165785420","https://openalex.org/W7166086163","https://openalex.org/W7166741545","https://openalex.org/W7166801116","https://openalex.org/W7166846344","https://openalex.org/W7166878968","https://openalex.org/W7167238575","https://openalex.org/W7167244192","https://openalex.org/W7167469073","https://openalex.org/W7167541061","https://openalex.org/W7168100836","https://openalex.org/W7168161033","https://openalex.org/W7168368334","https://openalex.org/W7168591366","https://openalex.org/W7169492487","https://openalex.org/W7169768884","https://openalex.org/W7170150187","https://openalex.org/W7203601225"],"related_works":["https://openalex.org/W7117251601","https://openalex.org/W7208815670","https://openalex.org/W7168633813","https://openalex.org/W7143663428","https://openalex.org/W4414161430","https://openalex.org/W7165017041","https://openalex.org/W4406150750","https://openalex.org/W4414085460","https://openalex.org/W4416161601","https://openalex.org/W7196946654"],"abstract_inverted_index":{"Metabolites":[0],"have":[1],"traditionally":[2],"been":[3],"viewed":[4],"primarily":[5],"as":[6,22,33,173],"energy":[7],"sources":[8],"and":[9,25,71,99,109,125,142,156,162,175,184,201,216,228],"biosynthetic":[10],"substrates":[11],"for":[12,159,165,198],"cells.":[13],"However,":[14],"the":[15,65,85,122,138,145,150,163,212],"discovery":[16,200],"of":[17,45,50,67,95,128],"novel":[18],"protein":[19,106],"modifications":[20,43],"such":[21,172],"lactylation,":[23],"succinylation,":[24],"O-GlcNAcylation":[26],"demonstrates":[27],"that":[28,56],"metabolites":[29],"can":[30],"also":[31],"function":[32],"signaling":[34],"molecules,":[35],"whose":[36],"activated":[37],"high-energy":[38],"derivatives":[39],"directly":[40],"drive":[41],"post-translational":[42],"(PTMs)":[44],"proteins.":[46],"The":[47],"regulatory":[48,80,101],"axis":[49],"\u2018metabolic":[51],"sensing\u2013PTM":[52],"remodeling\u2013cellular":[53],"functional":[54,126],"reprogramming\u2019":[55],"emerges":[57],"from":[58],"this":[59,79,129,209],"plays":[60],"a":[61],"significant":[62],"role":[63],"in":[64,154,157,170,204],"pathogenesis":[66],"tumors,":[68],"immune":[69],"disorders,":[70],"metabolic":[72,110,179,205],"genetic":[73],"diseases.":[74,206],"This":[75,131],"review":[76,210],"centers":[77],"on":[78,114,214],"axis.":[81,130],"We":[82],"first":[83],"elaborate":[84],"chemical-structural":[86],"basis":[87],"governing":[88,219],"metabolite-driven":[89,220],"PTM":[90],"biogenesis,":[91],"followed":[92],"by":[93],"discussion":[94],"upstream":[96],"metabolic-pathway":[97],"activation":[98],"downstream":[100,229],"outputs,":[102],"including":[103,137],"chromatin":[104],"remodeling,":[105],"phase":[107],"separation":[108],"feedback":[111],"circuits.":[112],"Based":[113],"this,":[115],"we":[116],"employ":[117],"cross-species":[118],"comparisons":[119],"to":[120,189,195,208],"discuss":[121],"evolutionary":[123],"conservation":[124],"divergence":[127],"analysis":[132],"clarifies":[133],"several":[134],"long-standing":[135],"controversies,":[136],"distinction":[139],"between":[140,147],"enzymatic":[141],"non-enzymatic":[143],"modifications,":[144,149],"crosstalk":[146],"different":[148],"concentration":[151],"thresholds":[152],"required":[153],"vivo":[155],"vitro":[158],"modification":[160],"occurrence,":[161,225],"strategies":[164],"validating":[166],"causality.":[167],"Finally,":[168],"advances":[169],"technologies":[171],"single-cell":[174],"spatial":[176],"multi-omics,":[177],"live-cell":[178],"probes,":[180],"targeted":[181],"small-molecule":[182],"tools,":[183],"systems":[185],"modeling":[186],"are":[187],"discussed":[188],"explore":[190],"their":[191,224],"potential":[192],"applications,":[193],"aiming":[194],"provide":[196],"insights":[197],"biomarker":[199],"precision":[202],"intervention":[203],"Central":[207],"is":[211],"emphasis":[213],"chemical":[215],"biophysical":[217],"constraints":[218],"PTMs,":[221],"which":[222],"shape":[223],"compartment-dependent":[226],"enzyme-dependence,":[227],"biological":[230],"outputs.":[231]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-11-07T00:00:00"}